Specificity of CD4+CD25+ regulatory T cell function in alloimmunity

Alberto Sánchez-Fueyo, Sigrid Sandner, Antje Habicht, Christophe Mariat, James Kenny, Nicolas Degauque, Xin Xiao Zheng, Terry B. Strom, Laurence A. Turka, Mohamed H. Sayegh

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

CD4+CD25+ regulatory T cells (TRegs) are critical for the acquisition of peripheral allograft tolerance. However, it is unclear whether TRegs are capable of mediating alloantigen-specific suppressive effects and, hence, contributing to the specificity of the tolerant state. In the current report we have used the ABM TCR transgenic (Tg) system, a C57BL/6-derived strain in which CD4+ T cells directly recognize the allogeneic MHC-II molecule I-Abm12, to assess the capacity of T Regs to mediate allospecific effects. In these mice, 5-6% of Tg CD4+ T cells exhibit conventional markers of the TReg phenotype. ABM TRegs are more effective than wild-type polyclonal TRegs at suppressing effector immune responses directed against I-Abm12 alloantigen both in vitro and in vivo. In contrast, they are incapable of suppressing responses directed against third-party alloantigens unless these are expressed in the same allograft as I-Abm12. Taken together, our results indicate that in transplantation, TReg function is dependent on TCR stimulation, providing definitive evidence for their specificity in the regulation of alloimmune responses.

Original languageEnglish
Pages (from-to)329-334
Number of pages6
JournalJournal of Immunology
Volume176
Issue number1
DOIs
StatePublished - 1 Jan 2006
Externally publishedYes

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